This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Symptomatic abnormalities of peripheral nerve function are among the most common complications of HIV-1 infection as HIV-sensory neuropathy (HIV-SN). There are presently no effective therapies for HIV-SN, and there are few animal models of HIV-SN in which candidate therapeutic agents can be tested. The CD8+ T lymphocyte depleted SIV-infected rhesus model, which is highly reproducible and results in rapid disease with consistent pathology will be used. Given that the CD8+ T lymphocyte depletion SIV infection model has close similarities to HIV-induced CNS disease and a high incidence of SIV encephalitis (SIVE) (~85%), we hypothesize that PNS lesions also develop at a high frequency, thus providing a model for the study of the mechanisms of HIV-SN disease. The main goal is to use the CD8+ T lymphocyte depletion SIV infection macaque model to determine the role of macrophage activation, monocyte traffic and virus driving peripheral nervous system (PNS) disease. The specific aim for this project is to define the role of resident macrophage activation, monocyte infiltration and virus in the development of HIV-induced PNS injury using CD8+ T lymphocyte depleted SIV infected rhesus macaques.